Pemetrexed Plus Bevacizumab Maintenance Keeps NSCLC at Bay Longer

October 2011, Vol 2, No 6

Stockholm, Sweden—Two expensive drugs may be better than 1 for maintenance treatment of advanced non– small-cell lung cancer (NSCLC), according to a study at the 2011 European Multidisciplinary Cancer Congress. Adding pemetrexed (Alimta) to bevacizumab (Avastin) maintenance therapy reduced the risk of disease progression in the phase 3 AVAPERL trial.

Pemetrexed is approved by the US Food and Drug Administration for the maintenance treatment of nonsquamous, locally advanced or metastatic NSCLC that has not progressed after 4 cycles of platinum-based chemotherapy. AVAPERL was the first phase 3 trial to investigate the combination of pemetrexed plus bevacizumab as maintenance therapy.

Patients receiving the combination had a median progression-free survival (PFS) of 10.2 months from the start of first-line induction therapy versus 6.6 months with single-agent bevacizumab maintenance, amounting to a 30% re duction in risk (P <.001), reported Fabrice Barlesi, MD, Assistance Publique Hôpitaux de Marseille, France. Similarly, from study randomization to maintenance therapy, median PFS was doubled with the combination: 7.4 months versus 3.7 months—a 52% reduction in risk (P <.001). Overall survival from induction was 15.7 months with single-agent bevacizumab and has not been reached with the combination used for maintenance.

“First-line cisplatin [Platinol], pemetrexed, and bevacizumab followed by continuation maintenance with bevacizumab and pemetrexed achieved a patient PFS benefit of unprecedented magnitude,” Dr Barlesi maintained.

All the 376 patients enrolled in AVAPERL received four 3-week cycles of first-line induction with bevacizumab, pemetrexed, and cisplatin. After this treatment, patients with a response or stable disease were randomized to continuation maintenance with bevacizumab (N = 125) or bevacizumab plus pemetrexed (N = 128). PFS was assessed from the beginning of induction therapy to progression or death.

Notably, grade 3-5 hematologic adverse events were greater with the bevacizumab plus pemetrexed arm, 10% versus 0% in the control arm. Grade 3-5 nonhematologic events were noted for 31% and 22%, respectively. —CH


New Warnings for Bevacizumab On September 30, 2011, the US Food and Drug Administration issued label changes for bevacizumab (Avastin), adding these 3 warnings: an increased risk for ovarian failure in premenopausal women who use the drug in combination with the mFOLFOX regimen; a risk for venous thromboembolism (VTE) and bleeding in patients using anticoagulation therapy after a first VTE event while receiving bevacizumab; and a risk for osteonecrosis of the jaw.

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